基因拷贝数变化在TEL/AML1+儿童急性白血病中作用的研究

项目名称： 基因拷贝数变化在TEL/AML1+儿童急性白血病中作用的研究

项目编号： No.81200396

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 张丽

作者单位： 中国医学科学院

项目金额： 23万元

中文摘要： 基因组内拷贝数变异(copy number variations，CNVs)可能是疾病机制的一个普遍来源。CNVs与自身免疫性疾病、感染性疾病等多种复杂疾病均有关，不仅影响疾病的易感性及发展进程，还可以通过影响药物代谢使个体的疗效产生差异。更为有意义的是，从基因拷贝数变异图谱与疾病的关联入手，找到了重大疾病的病因，促进了新药研究的发展。最近的基因组学研究显示：在儿童急性淋巴细胞白血病中，常发生涉及淋巴细胞分化及细胞周期调控的基因拷贝数的异常。众所周知，TEL/AML1+融合基因起源于宫内，仅有这一染色体易位不足以引起白血病，需要有"二次打击"才能致病。且TEL/AML1+急性淋巴细胞白血病的预后并不完全一致。本项目联合应用多重连接探针扩增技术以及单细胞定量多基因荧光原位杂交技术检测儿童TEL/AML1+ALL中多个常见基因拷贝数变化，研究基因拷贝数的变化与白血病发病机制及预后的相关性。

中文关键词： 儿童；白血病；淋巴细胞；急性；拷贝数变异

英文摘要： With the development of molecular biology techniques, submicrosopic structural variants have been found abundantly existing in human genome. The copy number variations (CNVs) are effecting genes expression and leading to the diversity of disease susceptibility,drug response and individual phenotype. Also of note, according to the relationship between CNVs and disease, the reason of some diseases had been found. Recently, more than 50 recurring genetic alteration have been identified in childhood acute lymphoblastic leukemia (ALL). These frequently involve genes with known or putative roles in lymphoid development and leukemogenesis. It is well known, that the TEL/AML1 fusion gene frequently originates before birth, probably as an initiation lesion. Additional, postnatal mutations are necessary for progression to overt malignancy. In addition, the outcome may be difference although the patients have the same risk group. We will evaluate Multiplex Ligation-dependent Probe Amplification (MLPA) and quantitative multigene fluorescence in situ hybridization (QM-FISH) on childhood ALL for the detection of the most common CNVs. Furthermore, we will study the role of CNVs in leukemogenesis and the outcome.

英文关键词： Pediatric；Acute；lymphoblastic；leukaemia；Copy number variations